Synthesis of 4′-aza analogues of 2′,3′-dideoxythymidine by 1,3-dipolar cycloadditions of nitrones to 1-N-vinyl-thymine

1,3-Dipolar cycloadditions: applications to the synthesis of antiviral agents

“…49 In previous works some isoxazolidines 31-35 (also called azadideoxynucleosides) were synthesized through the same route with identical objective, but the inhibition of HIV was only moderate. 50,51,52,53 In all cases, products 31-37 were obtained replication in the range of 100 μM. The particular conformation of 39 reduces the probability of puckering interconversion, which justify strongly the conserved DNAlike shape and therefore they could be considered for optimisation studies for designing more potent HCV reverse 75 transcriptase inhibitors.…”

“…drugs compatible with the side chain of all of the amino acids and the molecular dimensions of these heterocycles are somewhat similar to the amide bonds in terms of distance and planarity. These last two properties of 3 are closely related with the successful interaction with enzymes or even DNA or 50 RNA strands of the viruses in order to deter their proliferation. There is not vaccine or cure for HIV, and the most employed treatment consists of highly active antiretroviral therapy.…”

“…The present and the future of these antiviral tools has 50 been reported since the pharmacological point of view of pathogenic specific drugs such as amantidine, Tamiflu ® , and Relenza ® or ribavirin and interferons targeted against influenza or hepatitis C viruses, respectively. 3 Unfortunately, extensive data on their efficacy are not available and recent 55 reports of drug resistance in patients infected with, for example, H5N1 raise serious concerns.…”

“…86 The results were very promising against HIV, 78 (n = 1) being the most effective and less cytotoxic drug. 89 The connection of oxygen and nitrogen atoms provided a possibility to introduce 50 the nucleophilic nitrogen into the furanose ring with a minimum of steric manipulation, providing opportunities to modify the furanose ring of nucleoside analogues with novel structural features. Consequently, it became possible to design other related N,O-containing derivatives for biological 55 studies.…”

From sugars to modified nucleosides

“…19,[29][30][31] This approach should be a highly promising reaction for the straightforward synthesis of a variety of isoxazolidinyl nucleosides. The first chiral version of that reaction has been investigated by Merino.…”